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环状 RNA-001241 通过海绵吸附 miR-21-5p 并调节 TIMP3 表达来介导肝癌细胞对索拉非尼的耐药性。

CircRNA-001241 mediates sorafenib resistance of hepatocellular carcinoma cells by sponging miR-21-5p and regulating TIMP3 expression.

机构信息

Department of General Surgery, Guizhou Provincial People's Hospital, Guizhou 550000, China.

Department of General Surgery, Qinghai Provincial People's Hospital, Qinghai 810000, China.

出版信息

Gastroenterol Hepatol. 2022 Dec;45(10):742-752. doi: 10.1016/j.gastrohep.2021.11.007. Epub 2021 Dec 4.

Abstract

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and its incidence is on the rise, closely related to advanced liver disease. Sorafenib chemotherapy is one of the main treatment options for patients with advanced HCC. Despite several reports on HCC multidrug resistance, the underlying regulatory mechanisms are still unclear. In this study, we found circ-001241 was significantly upregulated in HCC tissues and cells. Knockdown of circ-001241 markedly inhibited HCC cell proliferation and decreased sorafenib-resistance. More importantly, circRNA acts as a ceRNA to suppress the expression and activity of miR-21-5p, leading to the increase in TIMP3 expression. In addition, circRNA-001241 facilitated HCC sorafenib-resistance by regulating the miR-21-5p/TIMP3 axis. Taken together, our study elucidated the oncogenic role of circ-001241 in mediating sorafenib resistance in HCC, providing insights and opportunities to overcome sorafenib resistance in patients with advanced hepatocellular carcinoma.

摘要

肝细胞癌 (HCC) 是全球主要的恶性肿瘤之一,其发病率呈上升趋势,与晚期肝病密切相关。索拉非尼化疗是晚期 HCC 患者的主要治疗选择之一。尽管有关于 HCC 多药耐药的几篇报道,但潜在的调节机制仍不清楚。在这项研究中,我们发现 circ-001241 在 HCC 组织和细胞中明显上调。circ-001241 的敲低显著抑制 HCC 细胞增殖并降低索拉非尼耐药性。更重要的是,circRNA 作为 ceRNA 抑制 miR-21-5p 的表达和活性,导致 TIMP3 表达增加。此外,circRNA-001241 通过调节 miR-21-5p/TIMP3 轴促进 HCC 索拉非尼耐药性。总之,我们的研究阐明了 circ-001241 在介导 HCC 索拉非尼耐药中的致癌作用,为克服晚期肝细胞癌患者的索拉非尼耐药提供了新的见解和机会。

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